Description / Table of Contents:
Summary At presently, the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are unknown. In recent years, the genetic background of hereditary motor neuron diseases has been partly defined. In particular, these advances represent an opportunity to improve our understanding of the pathogenesis of the familial and sporadic forms of ALS and thus provide a basis for rational therapeutic approaches. In this article, recent findings on the pathogenesis of the familial form of ALS and their implications for the sporadic form are discussed.

Notes:
Summary There is increasing evidence that the neurotoxic effects of excitatory amino acids and their analogues are part of the pathogenesis of neuronal degeneration in acute and chronic neurological disease. Recent studies indicate that activation of excitatory amino acid receptors is also induced in the mechanism of neuronal damage induced by impairment of cellular energy metabolism. This article briefly summarizes the evidence for the presence of such a mechanism and discusses metabolic diseases in which excitatory amino acids alone or in combination with energy deficiency could play a pathogenetic role. In these and other metabolic diseases, antagonists to excitatory amino acid receptors may offer a therapeutic opportunity; however, there are potential limits that may prevent chronic use.

Notes:
Abstract It is well accepted that excitotoxic mechanisms contribute to the pathogenesis of acute neuronal death in stroke, epilepsy, or brain trauma. It is less widely acknowledged that excitotoxic mechanisms play a role in the pathogenesis of chronic neurological disorders, in particular neurodegenerative diseases. However, evidence is accumulating that this mechanism is indeed part of the pathogenesis of late-onset neurodegenerative diseases. One of the clinical examples may be amyotrophic lateral sclerosis, a disease in which antiexcitotoxic strategies have neuroprotective effects in both, an established animal model and in man. In addition, there is accumulating neuropathological, pathobiochemical and pathophysiological evidence which indicates that excitotoxic mechanisms are part of the pathogenesis of the human disease and consequently part of the mechanisms explaining selective vulnerability (“pathoclisis”) in the human motor system.